Reducing events in patients with chronic heart failure (REDUCEhf ) study design: continuous hemodynamic monitoring with an implantable defibrillator.

BACKGROUND: The use of implantable cardioverter defibrillators (ICDs) has been proven effective in the prevention of sudden cardiac death (SCD) and constitutes standard of care in appropriate populations. Combining a pressure sensing system with ICD therapy represents the first attempt to provide continuous hemodynamic monitoring using a device previously designed exclusively for SCD protection. METHODS: REDUCE is a prospective, multicenter, randomized, single-blind, parallel-controlled trial designed to assess the safety of the Chronicle ICD system (single chamber ICD with a hemodynamic monitoring system) and the effectiveness of a management strategy guided by intracardiac pressure information among ICD-indicated New York Heart Association (NYHA) Class II or III heart failure (HF) patients. Those successfully implanted with a Chronicle ICD will be randomized to the Chronicle group or Control group. All patients will receive optimal medical therapy, but the hemodynamic information from the device will be used to guide patient management only in the Chronicle group. Primary endpoints include freedom from system-related complications and relative risk reduction of one or more HF-related events (hospitalizations, and emergency department and urgent care visits requiring intravenous therapy for HF). Approximately 850 patients will be enrolled in at least 75 centers in the United States to accrue the 419 events needed to test the primary effectiveness endpoint. Enrollment began in April 2006, and is expected to end during 2009. CONCLUSION: REDUCE will assess the safety of the Chronicle ICD system and the effectiveness of a patient management strategy based on remote access to continuous intracardiac pressures in reducing HF-related events.

The State of the Science on Integrating Palliative Care in Heart Failure.

BACKGROUND: Heart failure (HF) is a chronic progressive illness associated with physical and psychological burdens, high morbidity, mortality, and healthcare utilization. Palliative care is interdisciplinary care that aims to relieve suffering and improve quality of life for persons with serious illness and their families. It is offered simultaneously with disease-oriented care, unlike hospice or end-of-life care. Despite the demonstrated benefits of palliative care in other populations, evidence for palliative care in the HF population is limited. OBJECTIVE: The objective of this article is to describe the current evidence and the gaps in the evidence that will need to be improved to demonstrate the benefits of integrating palliative care into the care of patients with advanced HF and their family caregivers. METHODS: We reviewed the literature to examine the state of the science and to identify gaps in palliative care integration for persons with HF and their families. We then convened an interdisciplinary working group at an NIH/NPCRC sponsored workshop to review the evidence base and develop a research agenda to address these gaps. RESULTS: We identified four key research priorities to improve palliative care for patients with HF and their families: (1) to better understand patients' uncontrolled symptoms, (2) to better characterize and address the needs of the caregivers of advanced HF patients, (3) to improve patient and family understanding of HF disease trajectory and the importance of advance care planning, and (4) to determine the best models of palliative care, including models for those who want to continue life-prolonging therapies. CONCLUSIONS: The goal of this research agenda is to motivate patient, provider, policy, and payor stakeholders, including funders, to identify the key research topics that have the potential to improve the quality of care for patients with HF and their families.

Intracardiac Pressures Measured Using an Implantable Hemodynamic Monitor: Relationship to Mortality in Patients With Chronic Heart Failure.

BACKGROUND: The purpose of this analysis was to examine whether implantable hemodynamic monitor-derived baseline estimated pulmonary artery diastolic pressure (ePAD) and change from baseline ePAD were independent predictors of all-cause mortality in patients with chronic heart failure. METHODS AND RESULTS: Retrospective analysis used data from 3 studies (n=790 patients; 216 deaths). Baseline ePAD was related to mortality using a multivariable model including baseline and demographic data. Changes in ePAD defined as change from baseline to 6 months and from baseline to 14 days before death or exit from study were related to subsequent mortality, and analysis was adjusted for baseline ePAD. Area under the pressure versus time curve during 180 days before death or exit from study was related to mortality. Baseline ePAD, independent of other covariates, was a significant predictor of mortality (hazard ratio=1.07; 95% confidence interval=1.05-1.09; P<0.0001). Change in ePAD was an independent predictor of mortality (hazard ratio=1.07; 95% confidence interval=1.05-1.100; P=0.0008). Increased ePAD of 3, 4, or 5 mm Hg from baseline to 6 months was associated with increased mortality risk of 23.8%, 32.9%, or 42.8%. Change in ePAD from baseline to 14 days before death or exit from study was higher in patients who died (3.0±8 versus 1.7±10 mm Hg; P=0.003). Area under the pressure versus time curve in the final 180 days before death or exit from study was higher in patients who died versus those alive at end of study (185±668 versus 17±482 mm Hg.days; P=0.006). CONCLUSIONS: Implantable hemodynamic monitor-derived baseline ePAD and change from baseline ePAD were independent predictors of mortality in chronic heart failure patients.

Heart failure and diabetes: collateral benefit of chronic disease management.

To test the hypothesis that a focus on heart failure (HF) care may be associated with inadequate diabetes care, the authors screened 78 patients (aged 64+/-11 years; 69% male) with diabetes enrolled in an HF disease management program for diabetes care as recommended by the American Diabetes Association (ADA). Ninety-five percent of patients had hemoglobin A1c levels measured within 12 months, and 71% monitored their glucose at least once daily. Most patients received counseling regarding diabetic diet and exercise, and approximately 80% reported receiving regular eye and foot examinations. Mean hemoglobin A1c level was 7.8+/-1.9%. There was no relationship between hemoglobin A1c levels and New York Heart Association class or history of HF hospitalizations. Contrary to the authors' hypothesis, patients in an HF disease management program demonstrated levels of diabetic care close to ADA goals. "Collateral benefit" of HF disease management may contribute to improved patient outcomes in diabetic patients with HF.

Prognosis and mechanism of death in treated heart failure: data from the placebo arm of Val-HeFT.

The magnitude of benefit on mortality of combined angiotensin-converting enzyme inhibitor (ACEI) and beta-blocker (BB) therapy for heart failure cannot be reliably assessed from prospective randomized trials of individual drugs with intent-to-treat analysis. The placebo arm of the Valsartan Heart Failure Trial (Val-HeFT) included patients who remained on background therapy with ACEIs, BBs, neither, or both. The outcomes in these four subgroups should provide a better guide to mortality benefit. Overall mortality (mean follow-up, 23 months) was 31.6% in those receiving neither neurohormonal blocker, 29% and 39% lower in those on ACEIs or BBs, respectively, and 62% lower (11.9% mortality) in those receiving both drugs. In the neither neurohormonal inhibitor group, 48% of the heart failure-related deaths were adjudicated as sudden, whereas in the group receiving ACEIs and BBs, 79% of the deaths were sudden, and pump failure mortality was only 1% per year. The combination of ACEIs and BBs exerts a greater mortality reduction than suggested from clinical trials and reduces pump failure mortality to 1% per year.

Frequency and impact of delayed decisions regarding heart transplantation on long-term outcomes in patients with advanced heart failure.

OBJECTIVES: We sought to characterize decisions regarding listing of heart transplant candidates and to determine the impact of delayed listing for a transplant on survival. BACKGROUND: Evaluation and listing for heart transplantation have evolved over the past decade, with the complex decision process often extending beyond the time of initial review. Little is known about the current impact of decisions and timing of listing on outcomes. METHODS: Decisions were prospectively recorded during the initial committee discussions regarding patients referred for heart transplant evaluation. Survival and transplantation rates were assessed. RESULTS: A total of 214 patients were evaluated for heart transplantation (age 49 +/- 11 years, ejection fraction 21 +/- 9%, New York Heart Association class III +/- I, peak oxygen consumption 13 +/- 4 ml/kg/min). At the initial evaluation, 44% of patients were deemed eligible, 25% were potentially eligible, 19% were ineligible, and 12% were deferred. For eligible patients, 37% of patients were listed within 10 days of evaluation, and a total of 71% of patients were ever listed. Regardless of transplantation, the three-year survival rate in eligible patients not listed early was similar to that in patients listed immediately (85% vs. 77%, p = 0.34). Ineligible and potentially eligible patients had a higher three-year mortality rate than did eligible patients if transplantation occurred (51% vs. 17%, p < 0.001) or not (57% vs. 19%, p = 0.04). CONCLUSIONS: Using current accepted guidelines, many patients referred for transplant evaluation were not considered eligible for transplantation, and those who were eligible were not often listed immediately. Eligible patients not listed initially did well in the long term, and patients with relative contraindications had worse outcomes with or without a transplant.

Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status: a meta-analysis of major clinical trials.

OBJECTIVES: This study sought to assess the effect of angiotensin-converting enzyme (ACE) inhibitors and beta-blockers on all-cause mortality in patients with left ventricular (LV) systolic dysfunction according to gender, race, and the presence of diabetes. BACKGROUND: Major randomized clinical trials have established that ACE inhibitors and beta-blockers have life-saving benefits in patients with LV systolic dysfunction. Most patients enrolled in these trials were Caucasian men. Whether an equal effect is achieved in women, non-Caucasians, and patients with major comorbidities has not been established. METHODS: The authors performed a meta-analysis of published and individual patient data from the 12 largest randomized clinical trials of ACE inhibitors and beta-blockers to produce random effects estimates of mortality for subgroups. RESULTS: Data support beneficial reductions in all-cause mortality for the use of beta-blockers in men and women, the use of ACE inhibitors and some beta-blockers in black and white patients, and the use of ACE inhibitors and beta-blockers in patients with or without diabetes. Women with symptomatic LV systolic dysfunction probably benefit from ACE inhibitors, but women with asymptomatic LV systolic dysfunction may not have reduced mortality when treated with ACE inhibitors (pooled relative risk = 0.96; 95% confidence interval: 0.75 to 1.22). The pooled estimate of three beta-blocker studies supports a beneficial effect in black patients with heart failure, but one study assessing bucindolol reported a nonsignificant increase in mortality. CONCLUSIONS: Angiotensin-converting enzyme inhibitors and beta-blockers provide life-saving benefits in most of the subpopulations assessed. Women with asymptomatic LV systolic dysfunction may not achieve a mortality benefit when treated with ACE inhibitors.

Influence of healthy candidate bias in assessing clinical effectiveness for implantable cardioverter-defibrillators: cohort study of older patients with heart failure.

OBJECTIVE: To assess the potential contribution of unmeasured general health status to patient selection in assessments of the clinical effectiveness of implantable cardioverter-defibrillator (ICD) therapy. DESIGN: Retrospective cohort study. SETTING: Linked data from an ICD registry, heart failure registry, and Medicare claims data for ICDs implanted in 2005 through 2009. PARTICIPANTS: 29,426 patients admitted to hospital with heart failure aged 66 years or older and eligible for ICD therapy for primary prevention. MAIN OUTCOME MEASURES: Non-traumatic hip fracture, admission to a skilled nursing facility, and 30 day mortality-outcomes unlikely to be improved by ICD therapy. RESULTS: Compared with 17,853 patients without ICD therapy, 11,573 patients with ICD therapy were younger and had lower ejection fraction and more cardiac admissions to hospital but fewer non-cardiac admissions to hospital and comorbid conditions. Patients with ICD therapy had greater freedom from unrelated events after adjusting for age and sex: hip fracture (hazard ratio 0.77, 95% confidence interval 0.64 to 0.92), skilled nursing facility admission (0.53, 0.50 to 0.55), and 30 day mortality (0.12, 0.10 to 0.15). CONCLUSIONS: Lower risks of measured outcomes likely reflect unmeasured differences in comorbidity and frailty. The findings highlight potential pitfalls of observational comparative effectiveness research and support physician consideration of general health status in selecting patients for ICD therapy.

Link between decisions regarding resuscitation and preferences for quality over length of life with heart failure.

AIMS: Survival preferences, ascertained from time-trade-off utilities, have not been studied in heart failure patients who designate a 'do not resuscitate' (DNR) status. Therefore, the aim of this study was to determine the association of heart failure patients' resuscitation preferences with survival preferences and mortality in the ESCAPE trial. METHODS AND RESULTS: We analysed the association of resuscitation orders at 1 month with time-trade-off utilities and 6-month mortality. There were 26 and 349 patients with a DNR order and Full Code order, respectively. DNR patients were older, had more coronary artery disease, hypertension, renal impairment, and poorer exercise capacity than Full Code patients. DNR patients also experienced longer hospitalization and higher 6-month mortality. In multivariate analysis, DNR preference was associated with 10-fold higher odds of willingness to trade survival time (lower time-trade-off utility) in favour of improved quality of life [odds ratio 10.33, 95% confidence interval (CI) 1.65-64.80]. DNR preference was the best predictor of mortality (χ(2) 26.12, P < 0.0001, hazard ratio 6.88, 95% CI 3.28-14.41), despite adjustment for known predictors including brain natriuretic peptide. CONCLUSIONS: Heart failure patients' requests to forego resuscitation may signify more than simply 'what-if' directives for emergency care. DNR decisions may reflect preferences for intervention to enhance quality rather than prolong survival, which is particularly important as these patients have high early mortality.

Hospitalization for Heart Failure in the Elderly.

People over 65 years account for more than 80% of heart failure hospitalizations, with almost half in patients morer than 75. Heart failure hospitalizations accounted for 21% of the annual health care budget for a representative senior program. Heart failure with preserved ejection fraction accounts for over half of heart failure hospitalizations in the elderly. Current therapy for the elderly is directed to relieve congestion by reducing volume overload and hypertension, while addressing exacerbating factors such as ischemia and anemia. Heart rate reduction is critical when sinus rhythm cannot be maintained but can also improve diastolic filling during sinus rhythm. While cardiac transplantation is rarely indicated, other interventions should be actively considered. Most elderly patients admitted with heart failure wish resuscitation. As heart failure progresses, decisions regarding implantable defibrillators or dialysis require careful consideration, and the risk/benefit balance may shift toward therapies to improve quality of life. (c)1999 by CVRR, Inc.